Unknown Circovirus in Immunosuppressed Patient with Hepatitis, France, 2022.

Hepatitis of undetermined origin can be caused by a wide variety of pathogens, sometimes emerging pathogens. We report the discovery, by means of routine shotgun metagenomics, of a new virus belonging to the family Circoviridae, genus Circovirus, in a patient in France who had acute hepatitis of unknown origin.

Securing Wider EU Commitment to the Elimination of HCV.

In 2016, the Hepatitis B and C Public Policy Association (HepBCPPA), gathered all the main stakeholders in the field of hepatitis C virus (HCV) to launch the now landmark HCV Elimination Manifesto, calling for the elimination of HCV in the EU by 2030. Since then, many European countries have made progress towards HCV elimination. Multiple programs - from the municipality level to the EU level - were launched, resulting in an overall decrease of viremic HCV infections and liver-related mortality. However, as of 2021, most countries are not on track to reach the 2030 HCV elimination targets set by the WHO. Moreover, the COVID-19 pandemic has resulted in a decrease in HCV diagnoses and fewer direct acting antiviral treatment initiations in 2020. Diagnostic and therapeutic tools to easily diagnose and treat chronic HCV infection are now well established. Treating all patients with chronic HCV infection is more cost-saving than treating and caring for patients with liver-related complications, decompensated cirrhosis or hepatocellular carcinoma. It is more important than ever to reinforce and scale-up action towards HCV elimination. Yet, efforts urgently need the dedicated commitment of policymakers at all governmental and policy levels. Therefore, the 3rd EU Policy Summit, held in March 2021, featured EU parliamentarians and other key decision makers to promote dialogue and take strides towards securing wider EU commitment to advance and achieve HCV elimination by 2030. We have summarized the key action points and report the 'Call-to-Action' statement supported by all the major relevant European associations in the field.

Early IFNß secretion determines variable downstream IL-12p70 responses upon TLR4 activation.

The interleukin-12 (IL-12) family comprises the only heterodimeric cytokines mediating diverse functional effects. We previously reported a striking bimodal IL-12p70 response to lipopolysaccharide (LPS) stimulation in healthy donors. Herein, we demonstrate that interferon ß (IFNß) is a major upstream determinant of IL-12p70 production, which is also associated with numbers and activation of circulating monocytes. Integrative modeling of proteomic, genetic, epigenomic, and cellular data confirms IFNß as key for LPS-induced IL-12p70 and allowed us to compare the relative effects of each of these parameters on variable cytokine responses. Clinical relevance of our findings is supported by reduced IFNß-IL-12p70 responses in patients hospitalized with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or chronically infected with hepatitis C (HCV). Importantly, these responses are resolved after viral clearance. Our systems immunology approach defines a better understanding of IL-12p70 and IFNß in healthy and infected persons, providing insights into how common genetic and epigenetic variation may impact immune responses to bacterial infection.

Prognosis of French COVID-19 patients with chronic liver disease: A national retrospective cohort study for 2020.

BACKGROUND & AIMS: The impact of chronic liver disease on outcomes in patients with COVID-19 is uncertain. Hence, we aimed to explore this association. METHODS: We explored the outcomes of all adult inpatients with COVID-19 in France, in 2020. We computed adjusted odds ratios to measure the associations between chronic liver disease, alcohol use disorders, mechanical ventilation and day-30 in-hospital mortality. RESULTS: The sample comprised 259,110 patients (median [IQR] age 70 (54-83) years; 52% men), including 15,476 (6.0%) and 10,006 (3.9%) patients with chronic liver disease and alcohol use disorders, respectively. Death occurred in 38,203 (15%) patients, including 7,475 (28%) after mechanical ventilation, and 2,941 (19%) with chronic liver disease. The adjusted odds ratios for mechanical ventilation and day-30 mortality were 1.54 (95% CI 1.44-1.64, p <0.001) and 1.79 (1.71-1.87, p <0.001) for chronic liver disease; 0.55 (0.47-0.64, p <0.001) and 0.54 (0.48-0.61, p <0.001) for mild liver disease; 0.64 (0.53-0.76; p <0.001) and 0.71 (0.63-0.80, p <0.001) for compensated cirrhosis; 0.65 (0.52-0.81, p <0.001) and 2.21 (1.94-2.51, p <0.001) for decompensated cirrhosis; 0.34 (0.24-0.50; p <0.001) and 1.38 (1.17-1.62, p <0.001) for primary liver cancer; and 0.82 (0.76-0.89; p <0.001) and 1.11 (1.05-1.17; p <0.001) for alcohol use disorders. Chronic viral hepatitis; non-viral, non-alcoholic chronic hepatitis; organ, including liver, transplantation, and acquired immunodeficiency syndrome were not associated with COVID-19-related death. CONCLUSION: Chronic liver disease increased the risk of COVID-19-related death in France in 2020. Therapeutic effort limitation may have contributed to COVID-19-related death in French residents with a liver-related complication or an alcohol use disorder. LAY SUMMARY: We studied the outcomes, including mechanical ventilation and day-30 mortality, of all adults with COVID-19 who were discharged from acute and post-acute care in France in 2020 (N = 259,110). Patients with mild liver disease; compensated cirrhosis; organ, including liver, transplantation; or acquired immunodepression syndrome were not at increased risk of COVID-19-related mortality. Patients with alcohol use disorders, decompensated cirrhosis, or primary liver cancer were at increased risk of COVID-19-related mortality but were less likely to receive mechanical ventilation. Our results suggest that therapeutic effort limitation may have contributed to the excess mortality in French residents with a liver-related complication or an alcohol use disorder.

Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area.

BACKGROUND & AIMS: Patients affected by hepatocellular carcinoma (HCC) represent a vulnerable population during the COVID-19 pandemic and may suffer from altered allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of patients with HCC within 6 referral centres in the metropolitan area of Paris, France. METHODS: We performed a multicentre, retrospective, cross-sectional study on the management of patients with HCC during the first 6 weeks of the COVID-19 pandemic (exposed group), compared with the same period in 2019 (unexposed group). We included all patients discussed in multidisciplinary tumour board (MTB) meetings and/or patients undergoing a radiological or surgical programmed procedure during the study period, with curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treat. RESULTS: After screening, n = 670 patients were included (n = 293 exposed to COVID, n = 377 unexposed to COVID). Fewer patients with HCC presented to the MTB in 2020 (p = 0.034) and fewer had a first diagnosis of HCC (n = 104 exposed to COVID, n = 143 unexposed to COVID, p = 0.083). Treatment strategy was modified in 13.1% of patients, with no differences between the 2 periods. Nevertheless, 21.5% vs. 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared with 2019 (p <0.001). In 2020, 7.1% (21/293) of patients had a diagnosis of an active COVID-19 infection: 11 (52.4%) patients were hospitalised and 4 (19.1%) patients died. CONCLUSIONS: In a metropolitan area highly impacted by the COVID-19 pandemic, we observed fewer patients with HCC, and similar rates of treatment modification, but with a significantly longer treatment delay in 2020 vs. 2019. LAY SUMMARY: During the coronavirus disease 2019 (COVID-19) pandemic era, fewer patients with hepatocellular carcinoma (HCC) presented to the multidisciplinary tumour board, especially with a first diagnosis of HCC. Patients with HCC had a treatment delay that was longer in the COVID-19 period than in 2019.